Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression

Introduction. Obesity and related nonalcoholic fatty liver disease (NAFLD) are an emerging health care issue that imposes substantial morbidity to individuals. Growth and differentiation factor 15 (GDF15) limits food uptake, body weight, and energy balance by modulation of GDNF-family receptor α-lik...

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Main Authors: Timon E. Adolph, Felix Grabherr, Lisa Mayr, Christoph Grander, Barbara Enrich, Alexander R. Moschen, Herbert Tilg
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Obesity
Online Access:http://dx.doi.org/10.1155/2018/7108075
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author Timon E. Adolph
Felix Grabherr
Lisa Mayr
Christoph Grander
Barbara Enrich
Alexander R. Moschen
Herbert Tilg
author_facet Timon E. Adolph
Felix Grabherr
Lisa Mayr
Christoph Grander
Barbara Enrich
Alexander R. Moschen
Herbert Tilg
author_sort Timon E. Adolph
collection DOAJ
description Introduction. Obesity and related nonalcoholic fatty liver disease (NAFLD) are an emerging health care issue that imposes substantial morbidity to individuals. Growth and differentiation factor 15 (GDF15) limits food uptake, body weight, and energy balance by modulation of GDNF-family receptor α-like (GFRAL) signalling in the hindbrain. However, the regulation of GDF15 expression in obesity and NAFLD is incompletely understood. We sought to define the impact of weight loss achieved by laparoscopic adjustable gastric banding (LAGB) on hepatic and adipose GDF15 expression in a cohort of severely obese patients. Methods. We analysed GDF15 expression of liver and subcutaneous adipose tissue before and 6 months after LAGB in severely obese patients undergoing LAGB by quantitative real-time PCR. To assess the role of inflammation on GDF15 expression, we analysed Hep G2 hepatocytes stimulated with cytokines such as IL-1β, TNFα, IL-6, LPS, or cellular stressors such as tunicamycin. Results. GDF15 expression was mostly confined to the liver compared to adipose tissue in severely obese patients. Weight loss induced by LAGB was associated with reduced hepatic (but not adipose tissue) expression of GDF15. Stimulation with IL-1β or tunicamycin induced hepatic GDF15 expression in hepatocytes. In line with this, hepatic GDF15 expression directly correlated with IL-1β expression and steatosis severity in NAFLD. These data demonstrated that amelioration of metabolic inflammation and weight loss reduced hepatic GDF15 expression. Conclusion. Based on recent mechanistic findings, our data suggest that hepatic GDF15 may serve as a negative feedback mechanism to control energy balance in NAFLD.
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spelling doaj-art-eeeb15e48ebf4ac89f7c355b0df6d6392025-08-20T02:22:24ZengWileyJournal of Obesity2090-07082090-07162018-01-01201810.1155/2018/71080757108075Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 ExpressionTimon E. Adolph0Felix Grabherr1Lisa Mayr2Christoph Grander3Barbara Enrich4Alexander R. Moschen5Herbert Tilg6Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck 6020, AustriaIntroduction. Obesity and related nonalcoholic fatty liver disease (NAFLD) are an emerging health care issue that imposes substantial morbidity to individuals. Growth and differentiation factor 15 (GDF15) limits food uptake, body weight, and energy balance by modulation of GDNF-family receptor α-like (GFRAL) signalling in the hindbrain. However, the regulation of GDF15 expression in obesity and NAFLD is incompletely understood. We sought to define the impact of weight loss achieved by laparoscopic adjustable gastric banding (LAGB) on hepatic and adipose GDF15 expression in a cohort of severely obese patients. Methods. We analysed GDF15 expression of liver and subcutaneous adipose tissue before and 6 months after LAGB in severely obese patients undergoing LAGB by quantitative real-time PCR. To assess the role of inflammation on GDF15 expression, we analysed Hep G2 hepatocytes stimulated with cytokines such as IL-1β, TNFα, IL-6, LPS, or cellular stressors such as tunicamycin. Results. GDF15 expression was mostly confined to the liver compared to adipose tissue in severely obese patients. Weight loss induced by LAGB was associated with reduced hepatic (but not adipose tissue) expression of GDF15. Stimulation with IL-1β or tunicamycin induced hepatic GDF15 expression in hepatocytes. In line with this, hepatic GDF15 expression directly correlated with IL-1β expression and steatosis severity in NAFLD. These data demonstrated that amelioration of metabolic inflammation and weight loss reduced hepatic GDF15 expression. Conclusion. Based on recent mechanistic findings, our data suggest that hepatic GDF15 may serve as a negative feedback mechanism to control energy balance in NAFLD.http://dx.doi.org/10.1155/2018/7108075
spellingShingle Timon E. Adolph
Felix Grabherr
Lisa Mayr
Christoph Grander
Barbara Enrich
Alexander R. Moschen
Herbert Tilg
Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression
Journal of Obesity
title Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression
title_full Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression
title_fullStr Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression
title_full_unstemmed Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression
title_short Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression
title_sort weight loss induced by bariatric surgery restricts hepatic gdf15 expression
url http://dx.doi.org/10.1155/2018/7108075
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